The application represents an interdisciplinary approach to improving prevention, diagnosis, and treatment of prostate cancer. UCSF basic scientists and clinical investigators with diverse talents in cell and molecular biology, immunology, genetics, as well as informatics, biostatistics, and conducting phase I studies in prostate cancer are working together to address important problems in this disease. Four projects specifically are designed to improve treatment of advanced prostate cancer using either 1) anti-CTLA4 antibodies 2) mutant adenoviruses and radiation therapy, 3) recombinant human antibodies against prostate cancer antigens, and 4) mutant telomerases. One of the projects will identify new prostate cancer antigens using antibody gene diversity libraries and phage display. In addition, one project is focused on identifying the genetic aberrations in prostate cancer responsible for development and progression of the disease. A related project is focused on identifying modifier genes which determine whether patients develop prostate cancer metastases. Several Cores will provide critical support to the Projects including Cores focused on: Informatics, Clinical Research, Animal Technology; Tissue acquisition and storage, and Administration. In addition, members of a recently formed Prostate Cancer Advocacy Core will work with SPORE investigators to design, and implement optimal approaches to clinical trials.